Researchers at Albert Einstein College of Medicine of Yeshiva
University have found that overactivity of a brain enzyme may play a
role in preventing weight gain and obesity . The findings were reported
in Cell Metabolism.

To understand what drives hunger
and causes metabolic disease, many scientists have focused on the
hypothalamus, an almond-sized structure located deep within the brain
that controls body temperature, hunger, and thirst. Specialized nerve
cells in the hypothalamus sense whether the body contains adequate
amounts of nutrients and stored body fat. The cells then send out
signals telling other parts of the brain to adjust food intake,
metabolic rates, and physical activity accordingly -keeping the body's
caloric intake in balance with calories burned.

To learn more
about these nutrient-sensing pathways and how they go awry in metabolic
disorders, researchers at Einstein focused on an enzyme called p70 S6
Kinase 1, or S6K, which plays a role in regulating the growth and
proliferation of all cells, including nerve cells.

"It turns out
that this enzyme, and the pathway it regulates, is nutrient sensitive -
that is, S6K activity increases in the presence of carbohydrates and
protein," says the study's principal investigator, Gary J. Schwartz,
Ph.D., professor of medicine and neuroscience at Einstein. "This led us
to believe that S6K might not only be involved in maintaining the
structure and function of individual cells, but also in regulating the
energy balance of the whole body."

To test this hypothesis, the
researchers injected rats with special viruses that selectively raise
or lower S6K activity. The viruses were injected directly into the
lower-middle, or mediobasal, portion of the hypothalamus, an area rich
in nutrient-sensing nerve cells.

"When we raised the activity of
the enzyme, we saw reductions in food intake, in body weight, and in
production of peptides [small chains of amino acids] that normally
stimulate feeding," says Dr. Schwartz. "When we lowered S6K activity,
we saw essentially the opposite response."

The way increased S6K
activity reduced the rats' food intake is important, says Dr. Schwartz:
reducing the average size of meals rather than changing the number of
meals over the course of a day. So the animals apparently were sated
faster and therefore ate less at every meal.

In another
experiment, the researchers tested whether increased S6K activity would
protect against the natural tendency of mammals on a high-fat diet to
overeat. People deal with all those calories by putting on extra weight
and becoming insensitive to insulin - two of the hallmarks of metabolic
syndrome, a group of risk factors that raise the risk of heart disease
and type 2 diabetes.

When animals on a high-fat diet were given
the S6K-enhancing virus, they overate less and gained weight more
slowly than control animals, the researchers report. In addition, the
virus-enhanced animals had lower body-fat levels and better glucose
tolerance than the control group.

Overall, the study shows that
S6K acts as a kind of food-sensing thermostat in mammals, increasing or
decreasing feeding behavior and metabolism to maintain a normal energy
balance. "These findings show that it may be possible to control
obesity and other human metabolic disorders by developing drugs that
regulate S6K activity," says Dr. Schwartz.

Clémence Blouet,
Ph.D., a postdoctoral fellow at Einstein, is the lead author of the
paper. The other co-author is Hiraku Ono, Ph.D., also a postdoctoral
fellow at Einstein.

About Obesity

Obesity is a
condition in which the
natural energy reserve, stored in the fatty tissue of humans and other
mammals, exceeds healthy limits. It is commonly defined as a body mass
index (BMI) (weight divided by height squared) of 30 kg/m2
or higher. Although obesity is an individual clinical condition, some
authorities view it as a serious and growing public health problem.

A large number of medical conditions have been associated with obesity. Health consequences are categorized as being the result of
either increased fat mass (osteoarthritis, obstructive sleep apnea, social stigma) or increased number of fat cells (diabetes, cancer, cardiovascular disease, non-alcoholic fatty liver disease). Mortality is increased in obesity, with a BMI of over 32 being associated with a doubled risk of death. There are alterations in the body's response to insulin (insulin resistance), a proinflammatory state and an increased tendency to thrombosis (prothrombotic state).

Apart from the metabolic syndrome, obesity is also correlated
with a variety of other complications. For some of these complaints, it
has not been clearly established to what extent they are caused
directly by obesity itself, or have some other cause (such as limited
exercise) that causes obesity as well.
Health complications may include from this condition may include: